Immunotoxicity induced by Ivermectin is associated with NF-κB signaling pathway on macrophages

Ivermectin (IVM) has been widely used as a highly effective and broad-spectrum biopesticide in animal husbandry and agriculture. Considering the frequent environmental and occupational exposure, the various toxic effects caused by IVM should be paid more attention. The immune system is a common target of toxins due to its complexity and sensitivity. The toxicity effect of the immune system may lead to increased susceptibility to infections, with potentially fatal consequences. The immunotoxicity of IVM has received little attention, which poses a challenge to the systematic assessment of safety risks. The purpose of this study was to assess the immunotoxicity of the IVM using in vitro cellular assays. We proved that IVM could inhibit the cell viability, induce DNA damage and enhance apoptosis. In addition to the induction of cytotoxicity, IVM has also been shown to reduce the phagocytic capacity and significantly increase the mRNA expression levels of proinflammatory cytokines IL-6, IL-1 beta and TNF-alpha. Intracellular biochemical assay indicated that activation of the NF-kappa B signaling pathway, overproduction of reactive oxygen species (ROS), release of cytochrome C, DNA double strand damage. These results indicate that IVM can induce immunotoxicity through induction of immune dysfunction and cytotoxicity. In conclusion, this study supports that IVM can be immunotoxic to macrophages in different ways, and draw attention to the potential immunotoxicity of IVM.